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Bertocchini, F.

Publications and source records attributed to Bertocchini, F..

4 recordsLinked to original sources

Killing them softly with EPO: a new role for erythropoietin in the homeostasis of red blood cells

The regulation of red blood cell (RBC) homeostasis is widely assumed to rely on the control of cell production by erythropoietin (EPO) and the destruction of cells at a fixed, species-specific age. In this work, we show that such a regulatory mechanism is a poor homeostatic solution to satisfy the changing needs of the body. Effective homeostatic control requires RBC lifespan to be variable and tightly regulated. We show that EPO controls RBC lifespan by determining CD47 expression in newly formed RBCs and SIRP- expression in sinusoidal macrophages. EPO also controls the initiation and intensity of anti-RBC autoimmune responses that curtail RBC lifespan in some circumstances. These mechanisms continuously modulate the rate of RBC destruction depending on oxygen availability. The finding of new homeostatic roles for EPO and autoimmunity critically challenges the current paradigm of RBC homeostasis and sets the grounds for a new approach to this field.

physiology↗

The coordination of innate and adaptive immunity in bacteria

Bacteria have evolved a variety of innate and adaptive immune strategies to fight bacteriophage (phage) infections. Innate defenses (unspecific mechanisms directed against any phage infecting the cell) range from the identification and cleavage of the viral DNA by restriction nucleases to the suicidal death of infected host cells, an extreme solution that prevents the spread of the infection throughout the population. Adaptive immunity, on the other hand, involves the creation of an immune memory that targets specific phages in case of reinfection. It is obvious that not every infection leads to the suicide of the host cell or to the formation of immune memory against the infecting phage, so what determines the outcome of an anti-phage response? In this work, we suggest that the dynamic aspects of phage infections are key to addressing this question. We show that the rates of viral DNA replication and cleavage define functional categories of phages that differ in their susceptibility to the immune strategies evolved by bacteria. From this viewpoint, the combined action of diverse bacterial defenses would be necessary to reduce the chances of phage immune evasion. This perspective allows us to formulate simple molecular mechanisms that could account for the decision of infected cells to undergo suicidal cell death or to incorporate new phages into the immune memory. This work highlights the importance of dynamics to understand bacterial immunity and formulates explicit hypotheses that could inspire a new and original empirical approach to the study of phage/bacteria interactions.

microbiology↗

The virtualome: a computational framework toevaluate microbiome analyses

Microbiomes have been the focus of a substantial research effort in the last decades. The composition of microbial populations is normally determined by comparing DNA sequences sampled from those populations with the sequences stored in genomic databases. Therefore, the amount of information available in databanks should be expected to constrain the accuracy of microbiome analyses. Albeit normally ignored in microbiome studies, this constraint could severely compromise the reliability of microbiome data. To test this hypothesis, we generated virtualomes, virtual bacterial populations that exhibit the ecological structure of real-world microbiomes. Confronting the analyses of virtualomes with their original composition revealed critical issues in the current approach to characterizing microbiomes, issues that were empirically confirmed by analyzing the microbiome of Galleria mellonella larvae. To reduce the uncertainty of microbiome data, the effort in the field must be channeled towards significantly increasing the amount of available genomic information.

bioinformatics↗

Wax worm saliva and the enzymes therein are the key to polyethylene degradation by Galleria mellonella

Plastic degradation by biological systems with re-utilization of the by-products can be the future solution to the global threat of plastic waste accumulation. We report that the saliva of Galleria mellonella larvae (wax worms) is capable of oxidizing and depolymerizing polyethylene (PE), one of the most produced and sturdy polyolefin-derived plastics. This effect is achieved after a few hours exposure at room temperature and physiological conditions (neutral pH). The wax worm saliva can indeed overcome the bottleneck step in PE biodegradation, that is the initial oxidation step. Within the saliva, we identified two enzymes that can reproduce the same effect. This is the first report of enzymes with this capability, opening up the way to new ground-breaking solutions for plastic waste management through bio-recycling/up-cycling.

molecular biology↗